Genetic analysis of a nomadic tribe springs a surprise

They have a high genetic predisposition to Type 1 diabetes, but a very small number actually develop the disease.

Raikas
(Photo: Bharathi Ramasubban)

The Raikas of Rajasthan, a camel-rearing community living in the Thar desert, show a remarkably low incidence of Type 1 diabetes (T1D) compared to other Indian populations. Researchers expected that a genetic study of members of this tribe would demonstrate a similarly low incidence of certain genes commonly associated with the disease. Much to their surprise, the DNA of the community showed an unusually high frequency of these genes.

The human leukocyte antigen (HLA) system consists of a set of genes that play a key role in disease defence. The proteins they encode help the immune system to distinguish between proteins made by the body and those made by invading viruses or bacteria. This system can go wrong and cause the body to reject organ transplants, for instance. Certain HLA antigens also predispose people to autoimmune diseases like T1D and celiac disease. In particular, the HLA-DRB1*03 gene is associated with a high risk for the development of T1D in most populations, including Indians. “Sardinia (Italy) is a hotspot of this disease and the allelic frequency there is the highest in the world (55.7). 38.9 /100,000 Saridnians have T1D,” said Narinder K Mehra, who currently holds the Dr CG Pandit National Chair and is the Former Dean (Research) at the All India Institute of Medical Sciences (AIIMS), New Delhi.

Previous studies in the general North Indian population by Mehra and his team supported this strong association between gene and disease. The frequency of the gene was more than 85% in patients with T1D, compared to just 16-18% in a healthy sample. With this background in mind, researchers from AIIMS, led by Mehra and Uma Kanga, a Senior Research Scientist, studied the Raikas. Contrary to their expectations, however, at 53%, the allelic frequency in the Raikas was 2-3 times more compared to a non-Raika group living in the same region (~28%) and 3-4 times more compared to the North Indian population from Delhi (14.6%).

The researchers put forth several hypotheses that could explain the intriguing observations. “The Raika community is the only population in the world with such a high frequency of the DRB1*03 gene and such low occurrence of diabetes. This is where the role of environmental triggers may be coming into play,” said Mehra.

The Raikas lead an active lifestyle—most walk more than 10 kms everyday. They also get constant exposure to sunlight—Vitamin D is known to have protective effects against autoimmune disorders. Their staple diet consists of Bajra and camel milk. “Camel milk is known to be beneficial for T1D,” said Kanga. Chemical analysis by other research groups has shown that camel milk has some insulin-like properties. One of the authors of this study, RP Agarwal from SP Medical College, Rajasthan has independently conducted animal and clinical studies, which also support the anti-diabetic effect of camel milk. “In studies carried out over a period of 2 years, we have shown that the insulin requirement in children diagnosed with T1D goes down by 45% when camel milk was made part of their diets (>0.5 litres a day). In fact a handful of children do not require insulin to control blood sugar any more, just camel milk,” he said.

Another possibility that cannot be ruled out is that the Raikas could carry a protective gene that hasn’t been identified yet. “We did see some HLA genes in the community that are known to confer protection against T1D, but the frequency was not very high. We intend to carry the study forward and look for other genes (HLA and non-HLA) that may have a protective influence,” said Kanga.